This proposal represents a request for continued funding of the NIH-sponsored Clinical Pharmacology Fellowship Training Program at the Mayo Clinic-Mayo Clinic College of Medicine-Mayo Medical School. The foundation for this program is strong research training in state-of-the-art biomedical techniques as applied to human-drug interactions. The Mayo Clinical Pharmacology training experience includes a curriculum that systematically exposes Trainees to critical aspects of the science that underlies Clinical Pharmacology. At the heart of the training is an outstanding individual research experience within a supportive mentoring environment. Clinical Pharmacology is a bridge discipline devoted to the study of the interaction between drugs and biological systems. However, within the context of the ongoing revolution that is occurring in biomedical science, a revolution that promises to transform medical practice, Clinical Pharmacology lies at the confluence of molecular pharmacology, genomics, proteomics, bioinformatics and rational therapeutics-with an ultimate goal of truly individualized drug therapy. Specifically, Clinical Pharmacology seeks to enhance our understanding of the molecular basis for drug response and the application of that information at the translational interface to make it possible to tailor drug therapy to both he underlying disease process and the unique characteristics of each individual patient. Our ability to take advantage of the opportunity represented by the dramatic advances that are occurring in biomedical science to achieve those goals will require that we train a new generation of Clinical Pharmacologists in Systems Clinical Pharmacology. Large, comprehensive, integrated academic medical centers like the Mayo Clinic are ideally positioned to train this new generation of Clinical Pharmacologists. Mayo is able to do that because of its long history of the integration of basic and clinical medical research, because of a tradition of continuous contribution to the discipline of Clinical Pharmacology and because the Mayo Clinical Pharmacology Training Program has had decades of experience in successfully recruiting and training both physician scientists and laboratory-based translational scientists in Clinical Pharmacology. During the next funding cycle, the Mayo Clinical Pharmacology Fellowship Training Program will continue to emphasize strong laboratory-based research training in a supportive mentored environment joined with systematic exposure to developments in clinical science, with an emphasis on the rapidly evolving nature of biomedical science-all directed toward the goal of preparing each Fellow enrolled in the Program to become a future leader in Clinical Pharmacology.